CYP26C1

cytochrome P450 family 26 subfamily C member 1, the group of Cytochrome P450 family 26

Basic information

Region (hg38): 10:93060797-93069540

Links

ENSG00000187553 ∙ NCBI:340665 ∙ OMIM:608428 ∙ HGNC:20577 ∙ Uniprot:Q6V0L0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• focal facial dermal dysplasia type IV (Limited), mode of inheritance: AR
• focal facial dermal dysplasia type IV (Supportive), mode of inheritance: AR
• focal facial dermal dysplasia type IV (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Focal facial dermal dysplasia 4	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Dermatologic	16530710; 23161670

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CYP26C1 gene.

• Inborn genetic diseases (30 variants)
• not provided (15 variants)
• Optic nerve hypoplasia (2 variants)
• not specified (1 variants)
• Focal facial dermal dysplasia type IV (1 variants)
• Anophthalmia-microphthalmia syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CYP26C1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				6	3	9
missense			30	3	3	36
nonsense						0
start loss						0
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	1	0	30	9	6

Variants in CYP26C1

This is a list of pathogenic ClinVar variants found in the CYP26C1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-93061310-G-C			Likely benign (Mar 01, 2018)
10-93061329-G-T			Likely benign (Jan 23, 2018)
10-93061345-C-T			Likely benign (Dec 31, 2019)
10-93061384-C-T		not specified	Uncertain significance (Dec 21, 2022)
10-93061436-T-A		not specified	Uncertain significance (Nov 22, 2023)
10-93061447-A-T		CYP26C1-related disorder	Benign/Likely benign (May 22, 2023)
10-93062011-G-A		not specified	Uncertain significance (Aug 02, 2023)
10-93062121-C-G		not specified	Uncertain significance (Mar 20, 2023)
10-93062133-C-T		not specified	Uncertain significance (Aug 08, 2023)
10-93062161-A-C		Optic nerve hypoplasia	Likely benign (-)
10-93062169-C-T		not specified	Uncertain significance (Nov 10, 2022)
10-93062200-G-T		not specified	Uncertain significance (Aug 10, 2021)
10-93062210-C-G			Likely benign (Oct 10, 2018)
10-93062212-A-G		not specified	Uncertain significance (Sep 14, 2022)
10-93062224-G-T		not specified	Uncertain significance (Nov 27, 2023)
10-93062738-AGCCGCGCCGCGCTGGAGCGCTACGT-A			Pathogenic (Jun 28, 2022)
10-93062749-G-T		CYP26C1-related disorder	Likely benign (Apr 10, 2019)
10-93062754-A-C		not specified	Uncertain significance (Oct 29, 2021)
10-93062812-G-C		CYP26C1-related disorder	Likely benign (May 28, 2019)
10-93062819-G-A		not specified	Likely benign (Oct 25, 2023)
10-93062823-C-T			Benign (Dec 31, 2019)
10-93062837-G-C		not specified	Uncertain significance (Oct 25, 2022)
10-93062840-G-A		not specified	Uncertain significance (Feb 15, 2023)
10-93062862-G-T		not specified	Uncertain significance (Aug 11, 2022)
10-93062922-C-G		not specified	Uncertain significance (Aug 10, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CYP26C1	protein_coding	protein_coding	ENST00000285949	6	7434

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00164	0.974	125150	1	565	125716	0.00225

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0585	274	277	0.990	0.0000136	3219
Missense in Polyphen		120	117.65	1.0199		1409
Synonymous	1.54	109	132	0.829	0.00000668	1181
Loss of Function	1.97	7	15.3	0.457	7.17e-7	170

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000766	0.000765
Ashkenazi Jewish	0.00	0.00
East Asian	0.00121	0.00109
Finnish	0.00716	0.00719
European (Non-Finnish)	0.00320	0.00317
Middle Eastern	0.00121	0.00109
South Asian	0.0000328	0.0000327
Other	0.00231	0.00229

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays a role in retinoic acid metabolism. Acts on retinoids, including all-trans-retinoic acid (RA) and its stereoisomer 9-cis-RA (preferred substrate).
• Disease: DISEASE: Focal facial dermal dysplasia 4 (FFDD4) [MIM:614974]: A form of focal facial dermal dysplasia, a group of developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. Skin defects occur at the sites of facial fusion during embryogenesis, with temporal lesions situated at the junction between the frontonasal and maxillary facial prominences, and preauricular lesions at the meeting point of the maxillary and mandibular prominences. The ectodermal lesions show consistent histologic abnormalities: atrophy and flattening of the epidermis, replacement of the dermis by loose connective tissue, reduced levels of fragmented elastic tissue and absence of the subcutaneous tissues and adnexal structures. FFDD4 is characterized by isolated, preauricular skin lesions. {ECO:0000269|PubMed:23161670}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Retinol metabolism - Homo sapiens (human);Oxidation by Cytochrome P450;Metapathway biotransformation Phase I and II;Signal Transduction;Phase I - Functionalization of compounds;RA biosynthesis pathway;Vitamins;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;Signaling by Retinoic Acid;Signaling by Nuclear Receptors (Consensus)

Haploinsufficiency Scores

• pHI: 0.224
• hipred: Y
• hipred_score: 0.589

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.281

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cyp26c1
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; craniofacial phenotype; growth/size/body region phenotype; cellular phenotype

Zebrafish Information Network

• Gene name: cyp26c1
• Affected structure: pharyngeal arch
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: vitamin metabolic process;central nervous system development;anterior/posterior pattern specification;neural crest cell development;sterol metabolic process;retinoic acid catabolic process;organelle fusion;negative regulation of retinoic acid receptor signaling pathway;oxidation-reduction process
• Cellular component: endoplasmic reticulum membrane;integral component of membrane
• Molecular function: retinoic acid binding;iron ion binding;retinoic acid 4-hydroxylase activity;heme binding